Full and simplified assessment of left ventricular diastolic function in covid-19 patients admitted to ICU: Feasibility, incidence, and association with mortality.

PURPOSE: Left ventricular diastolic dysfunction (LVDD) is associated with poor outcomes in the intensive care unit (ICU). Nonetheless, precise reporting of LVDD in COVID-19 patients is currently lacking and assessment could be challenging. METHODS: We performed an echocardiography study in COVID-19 patients admitted to ICU with the aim to describe the feasibility of full or simplified LVDD assessment and its incidence. We also evaluated the association of LVDD or of single echocardiographic parameters with hospital mortality. RESULTS: Between 06.10.2020 and 18.02.2021, full diastolic assessment was feasible in 74% (n = 26/35) of patients receiving a full echocardiogram study. LVDD incidence was 46% (n = 12/26), while the simplified assessment produced different results (incidence 81%, n = 21/26). Nine patients with normal function on full assessment had LVDD with simplified criteria (grade I = 2; grade II = 3; grade III = 4). Nine patients were hospital-survivors (39%); the incidence of LVDD (full assessment) was not different between survivors (n = 2/9, 22%) and non-survivors (n = 10/17, 59%; p = .11). The E/e' ratio lateral was lower in survivors (7.4 [3.6] vs. non-survivors 10.5 [6.3], p = .03). We also found that s' wave was higher in survivors (average, p = .01). CONCLUSION: In a small single-center study, assessment of LVDD according to the latest guidelines was feasible in three quarters of COVID-19 patients. Non-survivors showed a trend toward greater LVDD incidence; moreover, they had significantly worse s' values (all) and higher E/e' ratio (lateral).

Real-world evaluation of the Stemoscope electronic tele-auscultation system.

BACKGROUND: With the spread of COVID-19, telemedicine has played an important role, but tele-auscultation is still unavailable in most countries. This study introduces and tests a tele-auscultation system (Stemoscope) and compares the concordance of the Stemoscope with the traditional stethoscope in the evaluation of heart murmurs. METHODS: A total of 57 patients with murmurs were recruited, and echocardiographs were performed. Three cardiologists were asked to correctly categorize heart sounds (both systolic murmur and diastolic murmur) as normal vs. abnormal with both the Stemoscope and a traditional acoustic stethoscope under different conditions. Firstly, we compared the in-person auscultation agreement between Stemoscope and the conventional acoustic stethoscope. Secondly, we compared tele-auscultation (recorded heart sounds) agreement between Stemoscope and acoustic results. Thirdly, we compared both the Stemoscope tele-auscultation results and traditional acoustic stethoscope in-person auscultation results with echocardiography. Finally, ten other cardiologists were asked to complete a qualitative questionnaire to assess their experience using the Stemoscope. RESULTS: For murmurs detection, the in-person auscultation agreement between Stemoscope and the acoustic stethoscope was 91% (p = 0.67). The agreement between Stemoscope tele-auscultation and the acoustic stethoscope in-person auscultation was 90% (p = 0.32). When using the echocardiographic findings as the reference, the agreement between Stemoscope (tele-auscultation) and the acoustic stethoscope (in-person auscultation) was 89% vs. 86% (p = 1.00). The system evaluated by ten cardiologists is considered easy to use, and most of them would consider using it in a telemedical setting. CONCLUSION: In-person auscultation and tele-auscultation by the Stemoscope are in good agreement with manual acoustic auscultation. The Stemoscope is a helpful heart murmur screening tool at a distance and can be used in telemedicine.

Long-term Cardiovascular Outcomes of Multisystem Inflammatory Syndrome in Children Associated with COVID-19 using an Institution Based Algorithm (preprint)

Background: Cardiovascular involvement is a major cause of inpatient and intensive care unit morbidity related to Multisystem inflammatory syndrome in children (MIS-C). The objective of this study was to identify long-term cardiovascular manifestations of MIS-C. Methods: We included 80 consecutive patients admitted to the intensive care unit with MIS-C who were evaluated for a year in our follow-up clinic using an institution protocol. The outcome measures were cardiac biomarkers (troponin and BNP), electrocardiogram changes, echocardiographic findings cardiovascular magnetic resonance (CMR) and graded-exercise stress test (GXT) findings. Results: The cohort included patients aged between 6 months and 17 years (median 9 years; 48.8% females). At the peak of the disease 81.3% had abnormal BNP and 58.8% had troponin leak which reduced to 33.8% and 18.8% respectively at discharge with complete normalization by 6 weeks post-discharge. At admission 33.8% had systolic dysfunction, which improved to 11.3% at discharge with complete resolution by 2 weeks. Coronary artery abnormalities were seen in 17.5% during the illness with complete resolution by 2 weeks post discharge except one (1.9%) with persistent giant aneurysm at 1 year-follow up. CMR was performed at 6 months in 23 patient and demonstrated 4 patients with persistent late gadolinium enhancement (17.4%). Normal exercise capacity with no ectopy was seen in the 31 qualifying patients that underwent a GXT. Conclusions: There is significant heterogeneity in the cardiovascular manifestations of MIS-C. Although majority of the cardiovascular manifestations resolve within 6 weeks, diastolic dysfunction, CAA and myocardial scar may persist in a small subset of patients warranting a structured long-term follow-up strategy.

The Relationship Between Brain Natriuretic Peptide (NT-proBNP) Levels and Diastolic Heart Failure in Patients With COVID-19 (preprint)

Background: Diastolic dysfunction has been reported in patients with COVID-19. Due to the role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the diagnosis of heart failure, this study investigated the relationship between serum NT-proBNP levels and diastolic heart failure in COVID-19 patients. Methods: : This descriptive-analytical study was performed at Ayatollah Rouhani Hospital in Babol. Fifty-four patients with confirmed COVID-19 diagnosis who were admitted to the ICU were included in the study. The primary outcome was the relationship and predictive role of NT-proBNP and diastolic heart failure in patients with severe SARS-COV-2 infection. Patients with pro BNP >125 pg/mL underwent echocardiography and the relationship between echocardiographic indices and NT-proBNP was assessed as a secondary outcome. Results: : Our study showed that plasma NT-proBNP levels in patients with increased diastolic dysfunction were associated with disease severity. It was also found that the cut-off point of NT-proBNP = 799 pg/mL could be a predictor of diastolic dysfunction grades two and three. In this study, patients with a serum NT-proBNP level equal or above 799 had 37 times higher chance of having diastolic dysfunction than those with a serum NT-proBNP level below 799. Patients with NT-proBNP above 556 had RV_EA> 2 in echocardiography, indicating increased right-sided filling pressures. Conclusion: Despite the confounding factors in the interpretation of the pro BNP level in COVID-19, its level can be used to estimate the presence of high-grade diastolic heart failure on the left and right sides of the heart and the presence of high filling pressures. Lower levels of NT-proBNP are associated with right-sided diastolic failure.

What might COVID-19 Patients Experience after Recovery? A Systematic Review (preprint)

Objectives: To determine post-COVID-19 complications after recovery and investigate the reported cases of re-infection. Methods: The researchers systematically reviewed three databases: PubMed, Google Scholar, and Word Health Organization (WHO) COVID-19 database looking for studies reported post-COVID-19 complications and COVID-19 reinfection. The search was conducted between November 21, 2020 and January 14, 2021. Inclusion criteria were articles written in English and had primary data. The studies reported the complications of COVID-19 after full recovery were included. Case reports were only included in the COVID-19 reinfection section. Results: The review included 69 studies related to post-COVID-19 complications and 13 case studies related to COVID-19 reinfection. Thirty-six studies reported post-cure respiratory complications including dyspnea to residual pulmonary fibrosis. Cardiac symptoms were reported in nine studies including palpitation, chest pain and diastolic dysfunction. Neurological complications included post-traumatic stress syndrome (PTSD), anxiety, depression, memory issues, insomnia and sleeping disturbance, cognitive impairments, and stigma. Gastrointestinal symptoms included nausea, vomiting, diarrhoea, and acute liver injury. Physical decline was the most common symptom reported in the musculoskeletal complications. Thirteen cases COVID-19 reinfection from nine countries were reported. Four patients had severe symptoms in the second infection while the symptoms of nine patient ranged from mild to moderate. The time taken for the reinfection ranged from 26 days to 145 days. Conclusion: COVID-19 may cause several types of complications after recovery. Lung abnormalities, neurological complications, and exercise intolerance were frequently identified complications among COVID-19 survivors. Reinfection can occur among COVID-19 survivors. Thus, COVID-19 may need long-term follow-up and should take preventive measures to prevent the reinfection.

Cardiometabolic Risks of SARS-CoV-2 Hospitalization Using Mendelian Randomization (preprint)

IntroMany cardiometabolic conditions have demonstrated associative evidence with COVID-19 hospitalization risk. However, the observational designs of the studies in which these associations are observed preclude causal inferences of hospitalization risk. Mendelian Randomization (MR) is an alternative risk estimation method more robust to these limitations that allows for causal inferences.Methods & materialsWe applied four MR methods (MRMix, IMRP, IVW, MREgger) to publicly available GWAS summary statistics from European (COVID-19 GWAS n=2,956) and multi-ethnic populations (COVID-19 GWAS n=10,808) to better understand extant causal associations between Type II Diabetes (GWAS n=659,316), BMI (n=681,275), diastolic and systolic blood pressure, and pulse pressure (n=757,601 for each) and COVID-19 hospitalization risk across populations. ResultsAlthough no significant causal effect evidence was observed, our data suggested a trend of increasing hospitalization risk for Type II diabetes (IMRP OR, 95% CI: 1.67, 0.96-2.92) and pulse pressure (OR, 95% CI: 1.27, 0.97-1.66) in the multi-ethnic sample. ConclusionsType II diabetes and Pulse pressure demonstrates a potential causal association with COVID-19 hospitalization risk, the proper treatment of which may work to reduce the risk of a severe COVID-19 illness requiring hospitalization. However, GWAS of COVID-19 with large sample size is warranted to confirm the causality.  

Bromodomain Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV2 Infection (preprint)

Cardiac injury and dysfunction occur in COVID-19 patients and increase the risk of mortality. Causes are ill defined, but could be direct cardiac infection and/or ‘cytokine-storm’ induced dysfunction. To identify mechanisms and discover cardio-protective drugs, we use a state-of-the-art pipeline combining human cardiac organoids with high throughput phosphoproteomics and single nuclei RNA sequencing. We identify that ‘cytokine-storm’ induced diastolic dysfunction can be caused by a cocktail of interferon gamma, interleukin 1β and poly(I:C) and also human COVID-19 serum. Bromodomain protein 4 (BRD4) is activated along with pathology driving fibrotic and induced nitric oxide synthase genes. BRD inhibitors fully recover function in hCO and totally prevent death in a cytokine-storm mouse model. BRD inhibition decreases transcription of multiple genes, including fibrotic, induced nitric oxide synthase and ACE2, and prevention of cardiac infection with SARS-CoV2. Thus, BRD inhibitors are promising candidates to prevent COVID-19 mediated cardiac damage.Funding: We acknowledge grant and fellowship support from the National Health and Medical Research Council of Australia (J.E.H., M.J.S., C.R.E., T.B.), Heart Foundation of Australia (J.E.H.), QIMR Berghofer Medical Research Institute (J.E.H.), The Stafford Fox Foundation (E.R.P.), the Royal Children’s Hospital Foundation (E.R.P.), Australian Research Council Strategic Initiative in Stem Cell Science (Stem Cells Australia) (E.R.P. and J.E.H.) and the Medical Research Future Fund (MRFF9200008) (J.E.H., T.B., M.J.S., K.P.A.MD., C.R.E., E.R.P.). M.J.S. is supported by Health and Medical Research Council of Australia Program (APP1132519) and Investigator (APP1173958) grants. A.S. is also supported by Investigator grant (APP1173880). The Murdoch Children’s Research Institute is supported by the Victorian Government’s Operational Infrastructure Support Program. This project received support from Dynomics Inc. J.E.H. is supported by a Snow Medical Fellowship. Conflict of Interest: R.J.M., J.E.H., G.A.Q.-R., D.M.T. and E.R.P. are listed as co-inventors on pending patents held by The University of Queensland and QIMR Berghofer Medical Research Institute that relate to cardiac organoid maturation and putative cardiac regeneration therapeutics. J.E.H. is a coinventor on licensed patents held by the University of Goettingen. R.J.M, E.R.P., D.M.T., B.G. and J.E.H. are co-founders, scientific advisors and stockholders in Dynomics Inc. D.M.T. and B.G. are employees of Dynomics Inc. /Dynomics Pty Ltd. QIMR Berghofer Medical Research Institute has filed a patent on the use of BRD inhibitors. Ethical Approval: Animal work was approved by the QIMR Berghofer Medical Research Institute Animal Ethics Committee. Ethical approval for the use of human embryonic stem cells (hESCs) was obtained from QIMR Berghofer’s Ethics Committee and was carried out in accordance with the National Health and Medical Research Council of Australia (NHMRC) regulations. Procedures complied with standards set under Australian guidelines for animal welfare and experiments were subject to Monash University animal welfare ethics review (Approval #MARP/2019/13606).